AIDSWEEKLY Plus, 6 May 1996 issue; Published by Charles Henderson, Publisher. Editorial & Publishing Office: P.O. Box 5528, Atlanta, GA 30307-0528 / Telephone: (800) 633-4931; Subscription Office: P.O. Box 830409, Birmingham, AL 35283-0409 / FAX: (205) 995-1588
Daniel J. DeNoon, Senior Editor

Subcutaneous inoculation with small amounts of antigen in combination with a steroid hormone induced common mucosal immunity in an animal model.

The immunomodulatory effect of the hormone, 1(alpha),25- dihydroxy vitamin D[3] (1,25(OH)[2]D[3]), was further increased by coadministration of dehydroepiandrosterone (DHEA).

"This novel immunization technique may afford new opportunities to effectively intervene in sexually transmitted diseases and other diseases caused by mucosal pathogens," reported University of Utah researcher Raymond A. Daynes and colleagues in the journal Infection and Immunity ("Induction of Common Mucosal Immunity by Hormonally Immunomodulated Peripheral Immunization," Infection and Immunity, 1996;64(4):1100-1109).

Especially via the action of secretory antibodies such as IgA, the common mucosal immune system is the most important means of defense against pathogens. Mucosal immune surveillance reduces the ability of a microbe to colonize mucosal surfaces, and secretory antibodies can neutralize toxins and microbial enzymes. IgA has also been shown to have intracellular antiviral activity.

But mucosal immunity is poorly understood, and the means of eliciting it are even less clear.

Because mucosally administered non-replicating antigens are inefficiently presented to induction sites for mucosal immunity, induction of common mucosal immunity has only been achieved by repeated administration of high doses of antigen with powerful adjuvants derived from mucosal pathogens such as cholera toxin or Escherichia coli enterotoxin.

Daynes et al. noted that both the quality and the quantity of immune response to antigen depends upon the types of cytokines produced in response to the antigen. They reasoned that they could manipulate cytokines to generate the types of effector immune responses usually seen in the Peyer's patch microenvironment within any secondary lymphoid organ.

They found that in situ exposure of lymph-node lymphocytes to 1,25(OH)[2]D[3] caused them to produce less gamma interferon and interleukin 2 (IL-2) and substantially more IL- 4, IL-5, and IL-10.

"When coupled with vaccination with hepatitis B surface antigen (HBsAg), the hormone-immunomodulated switch from a peripheral lymph-node phenotype to a Peyer's patch-like pattern promoted the induction of both a systemic and a common mucosal immune response," Daynes et al. reported.

"This was determined by the observed increased concentrations of serum anti-HBsAg antibody and by finding that anti-HBsAg secretory antibodies were detectable in urogenital, lachrymal, fecal, and oral secretions only in the hormone-treated animals."

Moreover, it appeared that the homing properties of hepatitis antigen-specific B cells were affected by the hormone: specific antibody-secreting cells could be detected in the lamina propria of the lungs and small intestines of hormone-treated animals after vaccination.

Addition of DHEA to the vaccine formulation containing 1,25(OH)[2]D[3] enhanced secretory antibody titers.

These findings outstripped the ability of the investigators to explain them.

"Unknown factors concerning the roles played by the mucosal lymphoid organs in B-cell differentiation into secretory antibody-producing cells still remain to be addressed," they admitted. "Clearly, additional work is necessary before we will fully understand the mechanisms operating to facilitate mucosal immunity following immunization under 1,25(OH)[2]D[3] influences."

Daynes et al. further reported an as-yet-unpublished finding: that mice were protected against herpes simplex 2 virus challenge by immunization with a DNA vaccine encoding the herpes glycoprotein D2 administered intramuscularly in the presence of 1,25(OH)[2]D[3] (Kriesel et al., J Inf Dis, in press).

"For some of the newly emerging vaccination strategies, it may ultimately prove difficult to use transmucosal immunization routes for effective mucosal vaccination," they wrote. "This may represent the case with nucleic acid vaccines, in which effective cellular transfection is required for protein antigen generation in vivo. Hormonally immunomodulated vaccination strategies could prove to be beneficial with this new form of immunization."

The corresponding author for this study is Raymond A. Daynes, Department of Pathology, University of Utah Medical School, Salt Lake City, Utah 84132. Phone: (801) 581-3013; Fax: (801) 581-8946; Email: (kimcash@medschool.med.utah.edu).

Copyright (c) 1995 - Charles Henderson, Publisher. All rights Reserved. Permission to reproduce granted to AEGIS by Charles W. Henderson. Authorization to reproduce for personal use granted granted by C. W. Henderson, Publisher, provided that the fee of US$4.50 per copy, per page is paid directly to the Copyright Clearance Center, 27 Congress Street, Salem, Massachusetts 01970, USA.

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Copyright © 1996 - Charles Henderson, Publisher. All rights Reserved. Permission to reproduce granted to AEGIS by Charles W. Henderson. Authorization to reproduce for personal use granted granted by C. W. Henderson, Publisher, provided that the fee of US$4.50 per copy, per page is paid directly to the Copyright Clearance Center, 27 Congress Street, Salem, Massachusetts 01970, USA.